Our group has three major research interests, HIV biology, Kaposi's sarcoma-associated herpesvirus biology, and pediatric HIV clinical research.[unreadable] In our HIV work, we are particularly interested in working to understand the involvement of host cell factors in HIV replication and the effects of HIV infection on the host cell. The hypothesis guiding much of our work holds that there is one set of cellular conditions that is ideal for normal cellular growth and replication, that another set of conditions is ideal for viral replication, and that viruses (particularly HIV) have evolved ways of altering their host cells to enhance viral replication.[unreadable] [unreadable] We have recently been exploring this hypothesis in two ways. First, we conducted a microarray study of cells latently infected with HIV that were induced into active replication. We found that during HIV replication the cellular gene expression pattern changed in a clear, temporally-ordered pattern. When we examined the cellular genes that showed differential expression during HIV replication, we noticed that some of the genes encoded proteins that were potentially targetable by available small molecule inhibitors. We are studying the ability of some of these agents directed against host cell functions to inhibit HIV replication, and obtained evidence that one approved drug, imatinib (Gleevec), could inhibit HIV replication. This discovery was the basis of a recent patent application.[unreadable] [unreadable] We also found, unexpectedly, that the cellular gene expression pattern of cell lines latently infected with HIV differed from the expression pattern of the cell lines' uninfected parental cells. We hypothesized that this difference in gene expression pattern occurred because, during the production of the latently infected cell lines, there was strong selection for the differential expression of cellular genes that tend to maintain HIV in latency. When we examined the genes that were differentially expressed in the latently infected we identified cellular genes that were potentially targetable by available small molecules. We hypothesized that treating the latently infected cells with these agents targeting the cellular genes differentially expressed in the latently infected cells would activate viral replication in the latently infected cells. We tested several agents that target the cellular genes differentially expressed in the HIV latently infected cells and found that the agents activated HIV out of latency, confirming our hypothesis. A key problem in HIV therapy is the persistence of reservoirs of cells latently infected with HIV that are unaffected by highly active antiretroviral therapy. The persistence of latent reservoirs of cells latently infected with HIV prevents HIV infection from being cured. The Identification of new, effective, non-toxic agents that activate HIV replication in latently infected cells may lead to the development of new strategies to deplete or eliminate the reservoir of latently infected cells, offering a potential approach to curing HIV infection. The new agents that activate HIV replication in latently infected cells were the subject of additional patent applications.[unreadable] [unreadable] The second way we are exploring the hypothesis that there is one set of cellular conditions that is ideal for normal cellular growth and replication, that another set of conditions is ideal for viral replication, and that viruses (particularly HIV) have evolved ways of altering their host cells to enhance viral replication is by studying the cellular genes that are differentially expressed when certain HIV genes are overexpressed. Recently, we focused on the gene encoding the HIV accessory protein Vpr. Vpr is an HIV protein that is not required for viral replication, but is required for a fully pathogenic HIV.